Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Role of Tumor-associated Macrophage in Tumor Microenvironment

암미세환경에서 종양관련대식세포의 역할

  • Min, Do Sik (Department of Molecular Biology, College of Natural Science, Pusan National University)
  • 민도식 (부산대학교 자연과학대학 분자생물학과)
  • Received : 2018.07.26
  • Accepted : 2018.08.22
  • Published : 2018.08.30
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Abstract

Cancer cells grow in an environment composed of various components that supports tumor growth. Major cell types in the tumor microenvironment are fibroblast, endothelial cells and immune cells. All of these cells communicate with cancer cells. Among infiltrating immune cells as an abundant component of solid tumors, macrophages are a major component of the tumor microenvironment and orchestrates various aspects of immunity. The complex balance between pro-tumoral and anti-tumoral effects of immune cell infiltration can create a chronic inflammatory microenvironment essential for tumor growth and progression. Macrophages express different functional programs in response to microenvironmental signals, defined as M1 and M2 polarization. Tumor-associated macrophages (TAM) secret many cytokines, chemokines and proteases, which also promote tumor angiogenesis, growth, metastasis and immunosuppression. TAM have multifaceted roles in the development of many tumor types. TAM also interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. TAM obtain various immunosuppressive functions to maintain the tumor microenvironment. TAM are characterized by their heterogeneity and plasticity, as they can be functionally reprogrammed to polarized phenotypes by exposure to cancer-related factors, stromal factors, infections, or even drug interventions. Because TAMs produce tumor-specific chemokines by the stimulation of stromal factors, chemokines might serve as biomarkers that reflect disease activity. The evidence has shown that cancer tissues with high infiltration of TAM are associated with poor patient prognosis and resistance to therapies. Targeting of TAM in tumors is considered a promising therapeutic strategy for anti-cancer treatment.

암세포는 종양의 성장을 지지하는 다양한 성분으로 구성되어 있는 환경에서 자란다. 암미세환경에 존재하는 주요 세포등은 섬유아세포, 내피세포, 면역세포들이며 이들세포들은 암세포들과 서로 소통을 하고 있다 종양조직에 유입된 면역세포중에서 대식세포가 종양미세환경의 주요성분으로서 다양한 면역현상들을 조절한다. 면역세포유입에 의한 암촉진과 항암효과 간의 복잡한 균형은 종양의 성장과 진행에 필요한 만성염증 환경을 생성시킬 수 있다. 대식세포는 M1과 M2 극성화로 규정된 미세환경 신호에 반응하여 기능적으로 다른 프로그램을 작동시킬 수 있다. 종양관련대식세포는 다양한 사이토카인, 케모카인, 단백질분해효소들을 분비함으로써 암 신생혈관형성, 증식, 전이 및 면역억제를 촉진시킨다. 최근에, 종양관련대식세포는 암줄기세포와 상호작용하여 종양의 진행, 전이 및 항암제 내성을 유도하는 것으로 알려져 있다. 종양관련대식세포는 암미세환경을 유지하기위해 면역억제 기능을 획득하며, 종양의 이질성과 가소성의 특성을 갖고 있어 암관련인자 및 감염등의 노출에 의해 서로 다른 극성형질로 리프로그래밍된다. 종양관련대식세포는 기질인자의 자극에 의해 암특이적인 케모카인들을 생성하기 때문에 케모카인은 질병의 활성을 반영하는 바이오마커로 작용할 수 있다. 종양조직에 종양관련대식세포가 많이 유입될수록 환자의 예후가 좋지 않으며 항암치료에 대한 저항성이 생긴다. 따라서 종양에서 대식세포를 표적화하는 항암치료는 유망한 치료전략이 될 수 있다.

Keywords

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